3 years ago
Genetic variation in the progesterone receptor gene and susceptibility to recurrent pregnancy loss: a case-control study
Touhami Mahjoub, Anis Haddad, Mariam Al-Mutawa, Wael Bahia, Wassim Y Almawi, Faouzi Janhani, Aymen Soua, Ramzi R. Finan
Objective
To investigate the association of progesterone receptor (PGR) gene variants with the susceptibility to recurrent pregnancy loss (RPL).
Design
Retrospective case-control study.
Setting
Outpatient obstetrics/gynecology clinics.
Population
Women with RPL (396), defined as ≥3 consecutive miscarriages of unknown etiology, and 361 control women.
Methods
PGR genotyping was done by allelic exclusion method (real-time PCR).
Main outcome measures
PGR SNPs and the distribution of their alleles, genotypes and haplotypes.
Results
Higher minor allele frequency (MAF) of rs590688, rs10895068, and rs1942836 was seen in RPL cases than in control women, which remained significant after controlling for multiple comparisons. Significantly higher frequencies of heterozygous (1/2) rs608995, along with heterozygous (1/2) and homozygous (2/2) rs590688, rs10895068, and rs1942836 genotype carriers were seen between RPL cases versus control women, respectively, which persisted after controlling for age, BMI, and menarche. Increased risk of RPL associated with rs590688 and rs1942836 was dependent on the number of minor alleles, thus suggesting a “dose-dependent” effect associated with both variants. Varied linkage disequilibrium (LD) was noted between rs590688, rs10895068, rs608995, and rs1942836 PGR variants associated with RPL. Increased frequency of CGTC, and reduced frequency of GGAT haplotypes was noted in women with RPL compared to control women, thereby assigning RPL susceptible and protective nature to these haplotypes, respectively. This association persisted after controlling for multiple comparisons, and adjusting for covariates.
Conclusions
This confirms positive association of specific PGR variants (rs590688, rs10895068, and rs1942836), and PGR haplotypes (ATGCCGTC, ATTCGGTC) with increased risk of RPL, thereby supports role for PGR as RPL candidate locus.
This article is protected by copyright. All rights reserved.
Publisher URL: http://onlinelibrary.wiley.com/resolve/doi
DOI: 10.1111/1471-0528.14949
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